Minimal residual disease in chronic myeloid leukaemia

The principle aim of residual disease analysis in patients with chronic myeloid leukaemia (CML) is to gauge patient response to treatment and, in patients after allogeneic BMT, to enable early diagnosis of relapse. RT-PCR is by far the most sensitive assay to detect residual disease in CML and can enable a single leukaemia cell to be detected in a background of 10(5)-10(6) normal cells. This is approximately 1000 x greater than the routine detection limit of the other methods. After allogeneic BMT, many CML patients are BCR-ABL positive for prolonged periods of time without subsequently relapsing. Thus the simple presence or absence of residual BCR-ABL transcripts in patients' leukocytes is of little value in the management of individual cases. Quantitative PCR techniques can distinguish between those PCR positive patients who have low or falling BCR-ABL levels on sequential analysis from those who have levels that are increasing. Provided assays are performed frequently enough, rising or persistently high numbers of BCR-ABL transcripts can be detected prior to frank relapse and this information may be used for early therapeutic intervention. Most patients who respond to treatment for relapse by donor lymphocyte infusion (DLI) achieve durable molecular remission. Quantitative PCR is also useful to gauge the response of CML patients to IFN-alpha. We have found that the great majority of patients in complete cytogenetic remission after treatment with IFN-alpha remain PCR positive and harbour a minority population of BCR-ABL positive myeloid precursor cells. It is unlikely therefore this treatment modality completely eliminates the disease in any patient.